Telomerase inhibition induces acute ATM-dependent growth arrest in human astrocytomas.
The purpose of the study was to examine the degree of hTERT, the catalytic subunit of telomerase, expression in paediatric high-grade astrocytoma and to explore the potential of telomerase inhibition as a therapy for these tumours. hTERT was expressed at high levels in 36 of 44 paediatric astrocytomas. Telomerase inhibition induced acute DNA damage and ATM-pathway-dependent G2/M cell cycle arrest in astrocytomas in vitro, both occurring prior to telomere shortening itself. Our data suggest that telomerase inhibition could be a useful adjuvant therapy for high-grade astrocytomas, potentially inducing tumour growth arrest following short-term treatment.
Wong
Vincent C H
VC
Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, Ont., Canada M5G 1X8.
Ma
Jing
J
Hawkins
Cynthia E
CE
D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology*; D064007:Ataxia Telangiectasia Mutated Proteins; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D002648:Child; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016615:Telomere / Q000502:physiology; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C509186:TERT protein, human; D019098:Telomerase